PT  - JOURNAL ARTICLE
AU  - D H Ho
AU  - N S Brown
AU  - A Yen
AU  - R Holmes
AU  - M Keating
AU  - A Abuchowski
AU  - R A Newman
AU  - I H Krakoff
TI  - Clinical pharmacology of polyethylene glycol-L-asparaginase.
DP  - 1986 May 01
TA  - Drug Metabolism and Disposition
PG  - 349--352
VI  - 14
IP  - 3
4099  - http://dmd.aspetjournals.org/content/14/3/349.short
4100  - http://dmd.aspetjournals.org/content/14/3/349.full
SO  - Drug Metab Dispos1986 May 01; 14
AB  - Polyethylene glycol (PEG)-L-asparaginase, at doses ranging from 500 to 8000 units/m2, was infused iv over 60 min in 31 patients of whom 27 were evaluable pharmacokinetically. The plasma disappearance of PEG-L-asparaginase is described by a monophasic curve with a mean half-life of 357 +/- 243 hr which is much longer than that of the unconjugated enzyme (half-life of approximately 20 hr). The rate of total clearance (128 +/- 74 ml/m2 X day) is much slower than that of L-asparaginase (2196 +/- 1098 ml/m2 X day). The volume of distribution is 2093 +/- 643 ml/m2, which is similar to that of L-asparaginase, indicating that PEG-L-asparaginase is mainly localized in the plasma. No enzyme could be measured in urine samples taken from nine patients for a period of up to 4 days. Additionally, no enzyme was measurable in one patient's pleural fluid obtained at the end of infusion and 6 days after infusion of a 1000-unit/m2 dose; the corresponding concentrations in plasma were 0.64 and 0.62 units/ml, respectively. In general, the plasma enzyme concentrations at the end of the 1-hr infusion and at 14 days after drug administration were proportional to the dose given. However, in two patients, a sudden disappearance of enzyme levels occurred which preceded anaphylactic reactions during subsequent treatment. A third patient developed severe bronchospasm 30 min after the first dose, but his enzyme levels were within the normal range.